Joslin Diabetes Center Launches National Clinical Trial To Explore If Anti-Inflammatory Drug Can Improve Glucose Control in Type 2 Diabetes

BOSTON — January 16, 2007 — Joslin Diabetes Center scientists are taking their groundbreaking research on the role of inflammation in type 2 diabetes to a new level this month with the launch of a national clinical trial to investigate whether salsalate, an anti-inflammatory drug used for years to manage arthritis pain, can reduce blood glucose levels in people with type 2 diabetes. If successful, the trial could lead one day to an inexpensive way to treat this most common form of diabetes, which has been increasing at epidemic rates in recent years.

About 800 adults with poorly controlled blood glucose levels are being sought to participate in the three-year study, referred to as Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D). The study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The study will be conducted at Joslin in Boston and at 15 other medical institutions across the nation.

"This is the first large-scale study in patients that tests whether reducing inflammation can actually be used to treat diabetes," says principal investigator Steven E. Shoelson, M.D., Ph.D., the Helen and Morton Adler Chair and Associate Director of Research at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School (HMS). "Given what we are learning about how type 2 diabetes develops, we think this might be getting at an underlying cause. We hope the study shows that targeting inflammation is a safe and inexpensive way to treat type 2 diabetes. We also hope that reducing inflammation decreases risk for coronary heart disease, which is another theory that we will be testing in a separate clinical study in the coming months."

In the United States, nearly 21 million people have diabetes. Type 2 diabetes accounts for about 90 to 95 percent of diagnosed cases, representing nearly 10 percent of the adult population. Type 2 diabetes, previously called adult onset or non-insulin dependent diabetes, is a disorder in which muscle and fat cells do not use insulin properly. Type 2 diabetes is closely linked to obesity and puts people who have the disease at greater risk for complications, including cardiovascular disease, blindness, kidney disease and amputations. People with type 2 diabetes die at rates two- to four-times higher than those who do not have diabetes.

"Sedentary lifestyle and western diet have been associated with obesity and diabetes," says co-principal investigator Allison B. Goldfine, M.D., Assistant Director of Clinical Research at Joslin and Assistant Professor of Medicine at HMS. "The study medication, salsalate, which is chemically similar to aspirin but has fewer side effects, has been used for more than 40 years in people to treat pain associated with arthritis. Recent studies in people show that salsalate may also lower blood glucose, but further testing needs to be done."

"The outcome of this study has the potential for significant public health benefit," said Dr. Myrlene Staten, NIDDK's Senior Advisor for Diabetes Translational Research. "If salsalate improves the control of type 2 diabetes, we would have an inexpensive addition to our arsenal of drug options."

In previous studies Drs. Shoelson and Goldfine and their collaborators found that inflammation — an immune system response that normally fights infection and promotes healing — plays a major role in the development of insulin resistance and type 2 diabetes. These researchers were the first to show that a major trigger of inflammation — the transcription factor NF-kB — is activated in fat and liver, perhaps providing the "missing link" between obesity and diabetes. In a real bench-to-bedside victory, the researchers built on these discoveries by conducting clinical trials in patients with diabetes, testing anti-inflammatory salicylates, which inhibit NF-kB, as insulin sensitizers. In these patients, blood glucose and lipid levels substantially decreased, glucose uptake and utilization improved, and liver glucose production increased. These studies laid the groundwork for the new clinical trial.

For the TINSAL-T2D study, the researchers are seeking adults ages 18 to 75 whose glucose levels are not in good control and who don't take insulin. Participants must be using no medication or be taking only one oral medication, or a low-dose combination of oral medications, among other criteria. Most participants can expect their involvement to last about six months.

Those volunteering to participate in the TINSAL-T2D study will undergo a variety of tests to determine if they are eligible. Participants selected for the study may receive either the study drug or a placebo. A placebo is an inactive pill that looks like the study drug, but a placebo contains no active medication. Placebos are used to determine if the results of the study are truly from the study drug. TINSAL-T2D study participants will receive all medication and treatments related to the study free of charge, and will continue to see their personal physician for all of their healthcare needs.

Other sites participating in the study include: Tulane University, New Orleans, LA; Kaiser Permanente, Atlanta, GA; MedStar Clinical Research Centers, Washington, D.C.; Kaleida Health’s Diabetes-Endocrinology Center of Western New York; North Shore Diabetes and Endocrine Associates, New Hyde Park, NY; Endocrine Clinical Research, Winter Park, FL; University of Rochester School of Medicine and Dentistry, NY. Additional sites anticipated include: University of North Carolina at Chapel Hill, NC; University of Nebraska Medical Center, Omaha, NE; Columbia University College of Physicians and Surgeons, New York City, NY; Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ; University of Illinois at Chicago, IL; Washington University in St. Louis School of Medicine, MO; Emory University School of Medicine, Atlanta, GA; and the University of Texas Southwestern Medical Center at Dallas, TX. For an updated list of site locations check out the TINSAL Web site at: http://www.tinsal-t2d.org/.